Continued efforts have been made to delineate the genetic mechanisms underlying virulence of rotavirus in the newborn gnotobiotic piglet model. In addition to the three genes encoding rotavirus outercapsid protein VP4 or VP7 or nonstructural protein NS28, a fourth gene (gene number three) encoding a core protein appears to play an important role in determining the virulence of rotavirus in the porcine model. Information obtained from this study may have important implications for the development of effective and safe rotavirus vaccine strategies.